TRAF family proteins
In accordance with the present invention, there are provided novel TRAF-Protein-Binding-Domain polypeptides (TPBDs). The invention also provides nucleic acid molecules encoding TPBDs, vectors containing these nucleic acid molecules and host cells containing the vectors. The invention also provides antibodies that can specifically bind to invention TPBDs. Such TPBDs and/or anti-TPBD antibodies are useful for discovery of drugs that suppress autoimmunity, inflammation, allergy, allograph rejection, sepsis, and other diseases.
1. A method of identifying an effective agent that modulates the association of a TPBD with a TRAF protein, comprising the steps of:
a) contacting said TPBD and TRAF proteins, under conditions that allow said TPBD and TRAF proteins to associate with an agent suspected of being able to modulate the association of said TPBD and TRAF proteins, wherein said TPBD is a polypeptide selected from the group consisting of SEQ ID NOS: 8, 10, 12, 23, 24, and 25; and
b) detecting the modulated association of said TPBD and TRAF proteins, wherein said modulated association identifies an effective agent.
2. The method of claim 1 , wherein said altered modulated association is detected by measuring the activity of NF-kB.
3. The method of claim 1 , wherein said modulated association is detected by measuring the activity of c-Jun N-terminal kinase.
4. The method of claim 1 , wherein said effective agent is a drug.
5. The method of claim 1 , wherein said effective agent is a protein.
6. The method of claim 1 , wherein said agent modulates TPBD association with a TNF family receptor or TPBD association with a TRAF-associated protein.
7. The method of claim 1 , wherein said agent modulates JNK activity.
8. The method of claim 1 , wherein said agent modulates NF-kB activity.
9. The mihod of claim 1 , wherein said TPBD sequence is SEQ ID NO:8.
10. The method of claim 1 , wherein said TPBD sequence is SEQ ID NO:10.
11. The method of claim 1 , vherein said TPBD sequence is SEQ ID NO:12.
12. The method of claim 1 , wherein said TPBD sequence is SEQ ID NO:23.
13. The method of claim 1 , wherein said TPBD sequence is SEQ ID NO:24.
14. The method of claim 1 , wherein said TPBD sequence is SEQ ID NO:25.